The objective of this proposal is to study effects of a contraceptive vaginal ring (CVR) on vaginal bacteria in women, and relate these changes to key measures of soluble mucosal host immune defense. We will build on limited data suggesting a favorable effect of CVR on vaginal bacteria, which comprise a critical first line of defense against infection with HIV and other sexually transmitted infections (STI). In Aim 1, we will determine the effect of the CVR on vaginal bacteria. The goal is to study whether sustained vaginal delivery of estrogen promotes healthy vaginal populations of desirable LB, and thus reduces risk of incident and persistent BV. Women with or at risk for BV will be enrolled and prior to CVR initiation will be assessed with bacterium-specific quantitative PCR (qPCR) assays for key lactobacilli and BV-associated bacteria (BVAB). After they initiate CVR, they will return monthly over 4 subsequent months for assessment. qPCR results will be used to determine how concentrations of vaginal bacteria change in presence of absence of CVR. We hypothesize that: CVR use will be associated with favorable vaginal change assessed by BVAB qPCR. In Aim 2, we will measure key parameters of the soluble mucosal host immune response and endocervical immune cell populations with CVR use, including restoration of protective immune mediators that are decreased in the setting of BV such as SLPI, defensins, and lactoferrrin, and reduction in pro- inflammatory cytokines and the number of activated T-cells in the endocervix. Endocervical swabs, cytobrushes and cervicovaginal lavage will be collected at each visit and concentrations of mediators measured. In Aim 3, we will evaluate incidence of lower genital tract infection, primarily BV, before and after establishment of the CVR. We hypothesize that CVR use will promote a desirable Lactobacillus-predominant, non-inflammatory vaginal environment with reduced frequency and quantity of BV.